TY - JOUR
T1 - MRI and pathology of REM sleep behavior disorder in dementia with Lewy bodies
AU - Murray, Melissa E.
AU - Ferman, Tanis J.
AU - Boeve, Bradley F.
AU - Przybelski, Scott A.
AU - Lesnick, Timothy G.
AU - Liesinger, Amanda M.
AU - Senjem, Matthew L.
AU - Gunter, Jeffrey L.
AU - Preboske, Gregory M.
AU - Lowe, Val J.
AU - Vemuri, Prashanthi
AU - Dugger, Brittany N.
AU - Knopman, David S.
AU - Smith, Glenn E.
AU - Parisi, Joseph E.
AU - Silber, Michael H.
AU - Graff-Radford, Neill R.
AU - Petersen, Ronald C.
AU - Jack, Clifford R.
AU - Dickson, Dennis W.
AU - Kantarci, Kejal
PY - 2013/11/5
Y1 - 2013/11/5
N2 - Objective: To determine structural MRI and digital microscopic characteristics of REM sleep behavior disorder in individuals with low-, intermediate-, and high-likelihood dementia with Lewy bodies (DLB) at autopsy. Methods: Patients with autopsy-confirmed low-, intermediate-, and high-likelihood DLB, according to the probability statement recommended by the third report of the DLB Consortium, and antemortem MRI, were identified (n = 75). The clinical history was assessed for presence (n = 35) and absence (n = 40) of probable REM sleep behavior disorder (pRBD), and patients' antemortem MRIs were compared using voxel-based morphometry. Pathologic burdens of phospho-tau, b-amyloid, and a-synuclein were measured in regions associated with early neuropathologic involvement, the hippocampus and amygdala. Results: pRBD was present in 21 patients (60%) with high-likelihood, 12 patients (34%) with intermediate-likelihood, and 2 patients (6%) with low-likelihood DLB. Patients with pRBD were younger, more likely to be male (p ≤ 0.001), and had a more frequent neuropathologic diagnosis of diffuse (neocortical) Lewy body disease. In the hippocampus and amygdala, phospho-tau and b-amyloid burden were lower in patients with pRBD compared with those without pRBD (p < 0.01). α-Synuclein burden did not differ in the hippocampus, but trended in the amygdala. Patients without pRBD had greater atrophy of temporoparietal cortices, hippocampus, and amygdala (p < 0.001) than those with pRBD; atrophy of the hippocampus (p = 0.005) and amygdala (p = 0.02) were associated with greater phospho-tau burdens in these regions. Conclusion: Presence of pRBD is associated with a higher likelihood of DLB and less severe Alzheimer-related pathology in the medial temporal lobes, whereas absence of pRBD is characterized by Alzheimer-like atrophy patterns on MRI and increased phospho-tau burden.
AB - Objective: To determine structural MRI and digital microscopic characteristics of REM sleep behavior disorder in individuals with low-, intermediate-, and high-likelihood dementia with Lewy bodies (DLB) at autopsy. Methods: Patients with autopsy-confirmed low-, intermediate-, and high-likelihood DLB, according to the probability statement recommended by the third report of the DLB Consortium, and antemortem MRI, were identified (n = 75). The clinical history was assessed for presence (n = 35) and absence (n = 40) of probable REM sleep behavior disorder (pRBD), and patients' antemortem MRIs were compared using voxel-based morphometry. Pathologic burdens of phospho-tau, b-amyloid, and a-synuclein were measured in regions associated with early neuropathologic involvement, the hippocampus and amygdala. Results: pRBD was present in 21 patients (60%) with high-likelihood, 12 patients (34%) with intermediate-likelihood, and 2 patients (6%) with low-likelihood DLB. Patients with pRBD were younger, more likely to be male (p ≤ 0.001), and had a more frequent neuropathologic diagnosis of diffuse (neocortical) Lewy body disease. In the hippocampus and amygdala, phospho-tau and b-amyloid burden were lower in patients with pRBD compared with those without pRBD (p < 0.01). α-Synuclein burden did not differ in the hippocampus, but trended in the amygdala. Patients without pRBD had greater atrophy of temporoparietal cortices, hippocampus, and amygdala (p < 0.001) than those with pRBD; atrophy of the hippocampus (p = 0.005) and amygdala (p = 0.02) were associated with greater phospho-tau burdens in these regions. Conclusion: Presence of pRBD is associated with a higher likelihood of DLB and less severe Alzheimer-related pathology in the medial temporal lobes, whereas absence of pRBD is characterized by Alzheimer-like atrophy patterns on MRI and increased phospho-tau burden.
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U2 - 10.1212/01.wnl.0000435299.57153.f0
DO - 10.1212/01.wnl.0000435299.57153.f0
M3 - Article
C2 - 24107861
AN - SCOPUS:84888220461
SN - 0028-3878
VL - 81
SP - 1681
EP - 1689
JO - Neurology
JF - Neurology
IS - 19
ER -